The 5HT1E serotonin receptor is one of fourteen serotonin receptors expressed in humans. It is especially highly expressed in human cortical brain tissue, indicating modulation of this receptor by drugs may produce robust effects on cognition and/or mood. There has been surprisingly little information on the inherent function of this receptor, presumably due to the lack of selective drugs to stimulate or antagonize the 5HT1E receptor. In order to advance the field of 5HT1E receptor pharmacology we propose to develop a high throughput screen (NTS) for selective agonists and antagonists for the human 5HT1E receptor. The specific aims of this proposal are to demonstrate that the recombinant cell line possesses the properties that will allow the application of HTS using SPA (Scintillation Proximity Assays) to the development of novel, specific agonists and antagonists for this understudied human brain serotonin receptor. Selective agonists and antagonists for the 5HT1E receptor should, at the least, provide information on the function of this highly expressed receptor, and may lead to novel therapeutics for brain dysfunction. [unreadable] [unreadable]